1. Field of the Invention
The present invention relates, in general, to a composition for treating a viral infection comprising Jab1. More particularly, the present invention relates to a composition for treating or preventing a viral infection comprising a Jab1 (Jun-activation binding protein 1) protein, a nucleic acid having a nucleotide sequence coding for a Jab1 protein or a recombinant virus expressing a Jab1 protein.
2. Description of the Related Art
Flavivirus and pestivirus belong to the Flaviviridae family which possesses a single-stranded positive sense RNA genome and causes various diseases in vertebrate hosts. West Nile virus (WNV) (Burt et al., Emerg Infect Dis., 8(8):820-826, 2002; Asnis et al., Clin Imfect Dis 30(3): 413-418, 2000) causes diseases including fever, rash, arthralgia and myalgia when infecting susceptible hosts. Apoptosis in wild-type WNV-infected brain cells is induced in a Bax-dependent manner (Parquet et al., FEBS Lett., 500(1-2):17-24. 2001), and the apoptosis is induced by the capsid protein of WNV through the mitochondrial/caspase-9 pathway (Yang et al., Emerg Infect Dis., 8(12):1379-1384, 2002). However, the intracellular pathological mechanism of West Nile virus infection has not been completely understood.
Immunoglobulins and antiviral agents such as interferon alpha-2b and ribavirin were conventionally used for preventing and treating West Nile virus infection (Agrawal and Petersen., J Infect Dis, 188(1):1-4, 2003; Morrey et al., Antiviral Res., 55(1):107-116, 2002; Anderson et al., Emerg Infect Dis., 8(1):107-108, 2002), but they have low therapeutic effects. At present, there is no effective drug for treating or preventing West Nile virus infection. Thus, there is a need for the development of such effective drugs.
On the other hand, Jab1 (Jun-activation binding protein 1) was initially known as a coactivator of AP-1 (Jun/Fos proto-oncogene) protein and has the following, various functions. Jab1 is a component (CSN5) of the COP9 signalosome (CSN) (Wei et al., Annu Rev Cell Dev Biol., 19:261-286, 2003), and Jab1/CSN5 exists in a wide spectrum of organisms, ranging from yeasts to plants and animals. Overexpression of Jab1 causes the translocation of cyclin dependent kinase inhibitor p27/Kip1 from the nucleus to the cytoplasm, accelerates the Ub-26S proteasome-dependent degradation, and participates in the G1-S transition of the cell cycle, mediated by p27/Kip1 (Tomoda et al., Nature, 398(6723):160-165, 1999). In addition, Jab1 involves the nuclear translocation of PGP9.5 that is overexpressed in primary lung cancer cells (Caballero et al., Oncogene, 21(19):3003-3010, 2002). Jab1 interacts with p53, Smad4 and lutropin/choriogonadotropin receptor and stimulates degradation of these proteins (Bech-Otschir et al., EMBO J., 20(6):1630-1639, 2001; Li et al. J Biol Chem., 275(18):13386-13393, 2000; Wan et al., EMBO J., 3(2):171-176, 2002). Taken together, Jab1 translocates proteins from the nucleus to the cytoplasm by interaction with intracellular proteins and thus stimulates protein degradation in a proteasome-dependent manner.
However, there is no report for interaction between Jab1 and viral proteins upon flavivirus infection.
Based on this background, the present inventors identified Jab1 as a protein interacting with the capsid protein of flavivirus, and found that Jab1 inhibits apotosis by accelerating degradation of the capsid protein and that Jab1 is useful for treating or preventing a viral infection, thereby leading to the present invention.